The Role of T Lymphocytes in the Pathogenesis of Hu Antibody Associated Paraneoplastic Neurological Syndromes

Paraneoplastic neurological syndromes (PNS) result from damage or dysfunction of the nervous system that is by definition not caused by tumor cell infiltration, infection, ischemia, metabolic and nutritional deficits, surgery or other forms of tumor treatment. Immunologic factors appear important in the pathogenesis of PNS because antineuronal antibodies against nervous system antigens have been defined for many of these disorders. The immunologic response is elicited by the ectopic expression of neuronal antigens by the tumor. Expression of these so-called ‘onconeural’ antigens is limited to the tumor and the nervous system. At the time of presentation of the neurological symptoms, most patients have not yet been diagnosed with cancer. Detection of paraneoplastic antibodies is extremely helpful in diagnosing an otherwise unexplained, and often rapidly progressive neurological syndrome as paraneoplastic. In addition, the paraneoplastic antibodies may also direct the search for an underlying neoplasm. The diagnosis and clinical management of PNS are reviewed in chapter 2. One of the most frequently involved solid tumors in PNS is small cell lung cancer (SCLC) and approximately 50% of patients with PNS and SCLC have high-titer Hu antibodies. This thesis focused on PNS that are associated with Hu-antibodies (Hu-PNS).

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